Effects of Metreleptin in Type 1 Diabetes Mellitus
This study will add leptin therapy to the current insulin therapy of Type 1 Diabetics with the aim of lowering the total insulin requirements and suppressing the steep fluctuations typically associated with Type 1 Diabetes.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Open Label Single Center Pilot Study to Study Teh Effects of Metreleptin Administration in Patients With Type 1 Diabetes Mellitus ( T1DM ).|
- Change in HgbA1c [ Time Frame: 5 months ] [ Designated as safety issue: No ]Improvement in HgbA1c over the course of 5 months of Leptin therapy.
- safety and tolerability of leptin in Type 1 Diabetic patients [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]To determine if adding leptin to insulin therapy will be safe and tolerated by type 1 diabetic patients.
- Mean and standard deviation of blood glucose [ Time Frame: 6 months ] [ Designated as safety issue: No ]To determine if there are changes in the mean blood glucose and the standard deviation of blood glucose as assessed by continuos glucose monitoring and frequent sampling.
- change in liver and muscle fat as measured by Liver and soleus triglycerides on MRS. [ Time Frame: 6 months ] [ Designated as safety issue: No ]Change in the soleus and liver Tg as measured by spectroscopy evaluated 4 times over the 6 months of therapy.
- Change in Glycomark [ Time Frame: Glycomark as measured at every visit from baseline until study end. ] [ Designated as safety issue: No ]Glycomark as a more sensitive measure of glycemic control.
|Study Start Date:||September 2010|
|Study Completion Date:||August 2014|
|Primary Completion Date:||January 2013 (Final data collection date for primary outcome measure)|
Experimental: active open label Leptin
Active open label Leptin for type 1 Diabetes
Drug: Leptin ( Metreleptin )
weight based sub-cutaneous injection twice daily of Leptin
The adipocyte hormone, leptin, has been shown to restore the health and glucoregulation of near-death, insulin deficient diabetic rodents. This makes leptin the only hormone, since the discovery of insulin in 1922, with this capability. Leptin normalizes the hyperglucagonemia of diabetes and reduces lipogenesis and cholesterologenenesis. Treatment of diabetic rodents with a combination of leptin and insulin, leads to a stable pattern of glucose control with reduced insulin requirements, as opposed to the high glucose variability that characterizes the treatment of type 1 diabetes with supraphysiologic doses of insulin alone. As such, we will initiate a pilot clinical trial to test combination leptin and insulin therapy in type 1 diabetes. Fifteen leptin sensitive patients (body mass index <27 kg/m²) with uncontrolled diabetes (HbA1c 7.0 to 10.0 %) will be treated with slightly supraphysiologic doses of recombinant human leptin (Amylin Pharmaceuticals). Subjects will be compared to themselves before and after treatment with leptin. Endpoint variables include HbA1c, change in daily insulin dose, mean and standard deviation of blood glucose from inpatient glucose monitoring and glucose meter download. We will also assess effects of leptin therapy on energy intake as assessed by 3-day food record and body weight and fat by DEXA. Intramyocellular and intrahepatic lipid concentration by 1H-MRS will be assessed before and after 3 months of metreleptin therapy. A satiety analysis will be employed. In addition, plasma hormones and inflammatory biomarkers will be assayed during the course of this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01268644
|United States, Texas|
|UT Southwestern Medical Center|
|Dallas, Texas, United States, 75390|
|Principal Investigator:||Abhimanyu Garg, M.D.||UT Southwestern Medical Center|